Breast Cancer (5)

Treatment


Hormone therapy includes tamoxifen and aromatase inhibitors. Tamoxifen competitively binds estrogen receptors. Aromatase inhibitors (anastrozole, exemestane, letrozole) block peripheral production of estrogen in postmenopausal women. Benefit of hormone therapy is greatest when tumors have estrogen and progesterone receptors, nearly as good when they have only estrogen receptors, minimal when they have only progesterone receptors, and absent when they have neither receptor. In patients with ER+ tumors, particularly low-risk tumors, hormone therapy may be used instead of chemotherapy. Aromatase inhibitors have recently been proven more effective than tamoxifen and are becoming the preferred treatment for early-stage breast cancer in receptor-positive postmenopausal patients. Adjuvant tamoxifen for 5 yr reduces annual odds of death by about 25% in premenopausal and postmenopausal women regardless of axillary lymph node involvement; treatment for 2 yr is not as effective, but treatment for > 5 yr has no advantage and may increase the likelihood that any recurrent cancer is tamoxifen-resistant. Letrozole may be used for postmenopausal women who have completed 5 yr of daily tamoxifen.

Tamoxifen can induce or exacerbate menopausal symptoms but reduces incidence of contralateral breast cancer and lowers serum cholesterol. Tamoxifen improves bone density in postmenopausal women, and there is some evidence of fracture reduction. Tamoxifen may reduce cardiovascular mortality risk. However, it significantly increases risk of developing endometrial cancer; reported incidence is 1% in postmenopausal women after 5 yr of use. Thus, if such women have spotting or bleeding, they must be evaluated for endometrial cancer. Nonetheless, the improved survival for women with breast cancer far outweighs increased risk of death due to endometrial cancer. Unlike tamoxifen, aromatase inhibitors do not cause menopausal symptoms, but they may increase risk of osteoporosis.

Metastatic disease: Any indication of metastases should prompt immediate evaluation. Treatment of metastases increases median survival by only 3 to 6 mo, although relatively toxic therapies (eg, chemotherapy) may palliate symptoms and improve quality of life; the decision to undergo treatment is highly personal.

Choice of therapy depends on the hormone-receptor status of the tumor, length of the disease-free interval (from diagnosis to manifestation of metastases), number of metastatic sites and organs affected, and patient's menopausal status. Most patients with symptomatic metastatic disease are treated with systemic hormone therapy or chemotherapy. Radiation therapy alone may be used to treat isolated, symptomatic bone lesions or local skin recurrences not amenable to surgical resection. Radiation therapy is the most effective treatment for brain metastases, occasionally achieving long-term control. Patients with multiple metastatic sites outside the CNS should initially be given systemic therapy. There is no proof that treatment of asymptomatic metastases substantially increases survival, and it may reduce quality of life.

Hormone therapy is preferred over chemotherapy for patients with ER+ tumors, a disease-free interval of > 2 yr, or disease that is not life threatening. Tamoxifen is often used first in premenopausal women. Ovarian ablation by surgery, radiation therapy, or use of a luteinizing-releasing hormone agonist (eg, buserelin, goserelin, leuprolide) is a reasonable alternative. Some experts combine ovarian ablation with tamoxifen therapy. If the cancer initially responds to hormone therapy but progresses months or years later, additional forms of hormone therapy may be used sequentially until no further response is seen. Aromatase inhibitors are being increasingly used as primary hormone therapy in postmenopausal women.

The most effective cytotoxic drugs for treatment of metastatic breast cancer are capecitabine, doxorubicin, gemcitabine, the taxanes paclitaxel and docetaxel, and vinorelbine. Response rate to a combination of drugs is higher than that to a single drug, but survival is not improved and toxicity is increased. Thus, some oncologists use single drugs sequentially.

For tumors with amplification of HER2/neu, the humanized monoclonal antibody trastuzumab is effective in treating and controlling visceral metastatic sites. It is used alone or with hormone therapy or chemotherapy.

About 10% of patients with bone metastases eventually develop hypercalcemia, which can be treated with IV bisphosphonates (eg, pamidronate).